We examined whether peripheral blood monocytes, lymphocytes, polymorphonuclear leukocytes, or eosinophils, obtained from individuals without known exposure to Giardia lamblia, exhibit antibody-dependent cellular cytotoxicity (ADCC) for this organism. Peripheral blood granulocytes but not lymphocytes from each individual were cytotoxic for G. lamblia in the presence of either human or rabbit anti-G. lamblia serum. At an effector to target ratio of 30:1, granulocyte cytotoxicity was 20% in the presence of human antiserum and 36% in the presence of rabbit antiserum. Granulocyte ADCC was concentration dependent with respect to antiserum and was not complement mediated. Most of the ADCC activity was mediated by polymorphonuclear neutrophils, and to a lesser extent by eosinophils. The predominant isotype of the antibodies sensitizing G. lamblia for granulocyte ADCC was IgG. We conclude that human peripheral blood granulocytes are cytotoxic for G. lamblia in the presence of IgG anti-G. lamblia antibodies. This activity, in addition to the previously observed spontaneous monocyte cytotoxicity, is likely to be an important mechanism for host defense against this parasite. © 1983.